Expert opinion on biological therapy
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Stroke is a major cause of mortality and disability in adults worldwide. Unfortunately, current therapy which targets vessel recanalization has a narrow treatment window, and at this time neuroprotective approaches are not effective for stroke treatment. However, after stroke the parenchymal and endothelial cells in the central nervous system (CNS) respond in concert to ischemic stressors and create a microenvironment in which successful recovery may ensue. Neurogenesis, synaptogenesis, axonal sprouting, glial cell activation, angiogenesis and vascular remodeling within the brain and the spinal cord are stimulated post stroke. Cell based-therapy amplifies these endogenous restorative effects within the CNS to promote functional outcome. ⋯ Experimental studies and clinical trials with cell-based therapy in stroke appear promising. Cell-based therapy is not intended for the replacement of damaged cells, but for the remodeling of the CNS by promoting neuroplasticity, angiogenesis and immunomodulation. However, there are risks associated with the use of cell-based therapy, and adequate evaluation of these potential risks is a prerequisite before clinical application for stroke patients.
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Expert Opin Biol Ther · Jul 2013
ReviewPharmacovigilance and biosimilars: considerations, needs and challenges.
Biosimilars are biologic medicines that are highly similar to approved biologics, notwithstanding minor differences in clinically inactive components. Since 2007, biosimilars have been approved for use in patients in the European Union (EU) and other regions. European experience provides several lessons as the United States (US) healthcare system prepares for biosimilar approvals. These lessons emphasize the need for adequate efficacy and safety studies, post-marketing surveys and a robust pharmacovigilance system that can accurately track and trace biologics, including biosimilars and their reference products, from the patient to the manufacturer. ⋯ The availability of biosimilars as lower-cost biologics must carefully consider issues of safety, efficacy and traceability. Stringent pharmacovigilance procedures are required to detect potential differences in safety signals between biosimilars and their reference products. Pharmacovigilance of biologics should include processes that are easily used by prescribing practitioners to ensure that data are consistent and new safety signals are properly reported and assigned to the correct product.
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Rituximab is a monoclonal antibody targeting CD20, used to treat B cell malignancies and B cell-mediated autoimmune diseases. Rituximab has the largest market of any monoclonal antibody therapeutic. Its patent will expire within the next few years and several manufacturers have already produced or are developing rituximab biosimilars that aim to match the innovator rituximab as closely as possible. ⋯ Cost is a key limitation of current biologics usage and there is a political impetus to the licensing of biosimilars. Concerns regarding potential dissimilarities of biosimilars are legitimate, but surmountable with techniques for in vitro, in vivo and clinical testing and more clearly defined regulatory requirements. These should provide reassurance to prescribers. However, the cost of manufacturing and licensing a biosimilar remains high and the reduction in cost may be more limited than for a non-biologic small molecule drug and its generic version. This cost reduction will be critical to the impact and use of rituximab biosimilars.
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Expert Opin Biol Ther · Jul 2013
ReviewBapineuzumab and solanezumab for Alzheimer's disease: is the 'amyloid cascade hypothesis' still alive?
The 'amyloid cascade hypothesis' remains the leading hypothesis to explain the pathophysiology of Alzheimer's disease (AD). Immunotherapeutic agents have been developed to remove the neurotoxic amyloid β42 protein and prevent the hypothesized amyloid β42-induced neurotoxicity and neurodegeneration. The most notable of these immunotherapies are bapineuzumab and solanezumab. ⋯ Phase III trials showed that bapineuzumab failed to improve cognitive and functional performances in AD patients, and was associated with a high incidence of amyloid-related imaging abnormalities (ARIA). Solanezumab's two Phase III trials in AD patients failed to meet endpoints when analyzed independently. However, analysis of pooled data from both trials showed a significant reduction in cognitive decline in mild AD patients. The improvement was associated with an increase in plasma amyloid-β (Aβ) levels and a low incidence of ARIA in solanezumab-treated patients. The marginal benefits of solanezumab are encouraging to support continued evaluation in future studies, and offer small support in favor of the ongoing viability of the 'amyloid cascade hypothesis' of AD.
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Expert Opin Biol Ther · Jun 2013
ReviewNew insights, recent advances, and current challenges in the biological treatment of multiple myeloma.
The availability of thalidomide, lenalidomide, and bortezomib has radically changed multiple myeloma (MM) treatment and significantly improved patients' outcome. Nevertheless, MM is still an incurable disease due to the development of resistance and relapse practically in all patients. Unraveling MM pathogenesis, identifying prognostically high-risk patient populations, and optimizing current treatment strategies are among the challenges we are facing to reach a cure for this disease. ⋯ Given continuing advances to overcome current treatment challenges in MM, we are confident that long-lasting responses can be expected in many of our patients within the next decade.